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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - Oncoworm (ONCOWORM: Using functional genomics in highly regenerative flatworms to find novel cancer genes)

Teaser

Summary

This project exploited the powerful planarian model system to achieve novel insights into the molecular processes underpinning oncogenesis and cancer. Based on the principle that biochemical and physiological functions of many genes are conserved across phyla we identified planarian genes that control the migration, proliferation and differentiation of the highly proliferative pluripotent adult stem cells (pASCs). We combined a bespoke specially designed partial irradiation assay, bioinformatic and expression based candidate gene identification and the capacity to perform RNAi based screens of gene function to identify novel genes controlling pASCs that are conserved in humans. Those novel genes of greatest promise can now be studied in mammalian cancer cell lines using the insights gleaned from planarians. This project brought together, for the first time, a world-class planarian laboratory with an eminent cancer cell biologist, Dr Kosaka, who acquired all the expertise required to exploit the planarian system and at the same time transfer his extensive knowledge of cancer biology to the Aboobaker laboratory.
The overall objectives were

i) Provide new insights into the regulation of stem cell biology in planarians,
ii) Leverage of the planarian model to find new genes involved in human cancer,
iii) Direct transfer of this new knowledge to mammalian systems.

The output of this project will now integrate the planarian system with current mammalian cell based approaches to studying cancer.

Work performed

The project uncovered a number of novel genes that may have role in directing stem cell proliferation, and are hence pertinent to human cancer. These can now be studied in further detail to elucidate their roles.

In particular we found new genes that control stem cell proliferation in planarians, that have human counterparts that currently have no function assigned to them. These genes now represent important genes to study further, perhaps in mammalian systems.

Final results

We have developed novel phenotyping methods of stem cell behaviour to make best use of the planarians model system that will be of widespread use to the scientific community and generate new knowledge about how stem cells are regulated.